Bone modeling: biomechanics, molecular mechanisms, and clinical perspectives

Abstract

Abstract Bone modeling is a mechanically mediated adaptive process for changing a bone's size, shape, or position. Site specific, anabolic and catabolic modeling events are manifestations of overload hypertrophy and disuse atrophy, respectively. Catabolic bone modeling at the periodontal ligament (PDL) surface is the rate-limiting step in tooth movement. In initiating tooth movement, connective tissue growth factor (CTGF) is expressed in osteoblasts and osteocytes, and osteopontin (Opn) is expressed by osteoclasts and osteocytes. Undermining resorption occurs by recruiting osteoclasts to the site of maximal PDL compression and a paravascular osteogenic response is initiated in widened areas of the PDL: (1) preosteoblast formation at ∼10 hours, (2) peak DNA synthesis at ∼20 hours, (3) maximum rate of mitosis at ∼30 hours, and (4) initiation of bone formation at ∼48 hours. At other skeletal sites, additional genes have been linked to mechanical activation of bone: glutamate/aspartate transporter (GLAST), nitric oxide synthetase (NOS), prostaglandin G/H synthetase (PGHS-2), Msx1 , and c-fos . An intricate series of endocrine, paracrine, and autocrine factors has been described. Parathyroid hormone (PTH) enhances expression of insulin-like growth factor I (IGF-I) and the estrogen receptor beta (ER-β), which are both modulators of mechanical loading. Transforming growth factor beta (TGF-β) and the related bone morphogenetic proteins (BMPs) help control anabolic modeling. Catabolic modeling is mediated by PGE2, IL-1β, and other inflammatory cytokines. Osteoclast differentiation and activation is controlled by genes related to tumor necrosis factor (TNF) and its receptor (TNFR): colony stimulating factor 1 (CSF-1), osteoprotegerin (OPG), receptor activator of nuclear factor (RANK), and RANK ligand (RANKL). Orthodontic aspects of bone modeling are reviewed relative to morphology, biomechanics, neurology, molecular control mechanisms, and the periodontal adaptation to loading. Clinical correlations discussed are orthodontic analgesics, inflammatory cytokines, surgical enhancement of tooth movement, distraction osteogenesis, closure of atrophic defects, periodontal compromise, traumatized periodontium, and systemic disease.